McNamara Tanner A, Weng Hanyi, Liao Hsin Yu, Ito Rutsuko
Department of Psychology (Scarborough), University of Toronto, Toronto, ON, Canada.
Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada.
Sci Rep. 2025 Jan 23;15(1):2982. doi: 10.1038/s41598-024-82517-1.
Recent research has identified sex-dependent links between risk taking behaviors, approach-avoidance bias and alcohol intake. However, preclinical studies have typically assessed alcohol drinking using a singular dimension of intake (i.e. drinking level), failing to capture the multidimensional pattern of aberrant alcohol-seeking observed in alcohol use disorder. In this study, we sought to further explore individual and sex differences in the relationship between approach-avoidance bias, frontloading (bingeing and onset skew) and multiple addiction-like indices of ethanol seeking that included motivation for ethanol, persistence despite its absence (extinction), and ethanol-taking in the face of mild footshock. We found that female rats displayed more addiction-like phenotypes than males overall, and that frontloading patterns differed by sex, with females outdrinking males in the early part of access sessions (bingeing), but males strongly concentrating their lever pressing for ethanol in that period (onset skew). Multiple regression analyses revealed that bingeing was a strong positive predictor and onset skew a negative predictor of motivational breakpoint. Cued-conflict preference - a measure of approach-avoidance bias towards a mixed-valence conflict cue - was predictive of both extinction and footshock in males, but not females. Our data highlight key sex differences, and the relevance of both frontloading patterns and conflict preference in predicting future addiction-like phenotypes.
近期研究已确定冒险行为、趋近-回避偏向与酒精摄入量之间存在性别依赖性联系。然而，临床前研究通常使用摄入量的单一维度（即饮酒水平）来评估酒精饮用情况，未能捕捉到酒精使用障碍中观察到的异常酒精寻求的多维模式。在本研究中，我们试图进一步探讨趋近-回避偏向、前期负荷（暴饮和起始偏斜）与多种类似成瘾的乙醇寻求指标之间关系的个体差异和性别差异，这些指标包括对乙醇的动机、在乙醇缺失时的持续性（消退）以及面对轻度足部电击时的乙醇摄取。我们发现，总体而言雌性大鼠比雄性大鼠表现出更多类似成瘾的表型，并且前期负荷模式存在性别差异，雌性大鼠在获取阶段早期的饮酒量超过雄性大鼠（暴饮），但雄性大鼠在该时期强烈集中其对乙醇的杠杆按压行为（起始偏斜）。多元回归分析显示，暴饮是动机断点的强正向预测因子，起始偏斜是负向预测因子。线索冲突偏好——一种对混合效价冲突线索的趋近-回避偏向测量指标——在雄性大鼠中可预测消退和足部电击，但在雌性大鼠中则不然。我们的数据突出了关键的性别差异，以及前期负荷模式和冲突偏好在预测未来类似成瘾表型方面的相关性。
